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Key Researcher Agrees to Retract Both Disputed Stem Cell Papers

TOKYO—After several months of fiercely defending her discovery of a new, simple way to create pluripotent stem cells, Haruko Obokata of the RIKEN Center for Developmental Biology in Kobe, Japan, has agreed to retract the two Nature papers that reported her work.

Satoru Kagaya, head of public relations for RIKEN, headquartered in Wako near Tokyo, confirmed press reports today that Obokata had finally agreed to retract both papers. He said the institute would be notifying Nature and that the decision to formally retract the papers would be up to the journal.

Apparently all of the Japanese authors have now agreed to retract the two papers, which appeared as an article and a letter online in Nature on 29 January. But the position of co-authors based in the United States is unclear. And even if the papers are retracted, questions about the flawed technique and the way it ended on the pages of Nature remain to be answered.

In their two papers, Obokata and her colleagues described how briefly bathing blood cells from newborn mice in a mildly acidic solution and then carefully culturing them could generate pluripotent stem cells that could produce mouse embryos and even placentas. They dubbed their process stimulus-triggered acquisition of pluripotency, or STAP. Within a week of publication, science watchdogs started raising allegations of image manipulation and plagiarism.

Responding to the rising chorus of concern, RIKEN formed an investigative committee that documented numerous problems with the papers in a 14 March interim report. Its final report, published in April, concluded that at least two of these, both in the Nature article, constituted scientific misconduct. The report called for the article to be retracted.

Obokata refused to agree to retract the article and appealed the finding of misconduct. At a 9 April press conference, she acknowledged making mistakes but claimed they were the result of inexperience and were not intended to mislead. On 8 May, the RIKEN panel upheld the misconduct finding. A disciplinary committee is now deliberating possible punishments for Obokata and her co-authors.

But allegations surrounding the papers have continued to accumulate. Last week, Japanese media reported that two images in the Nature letter supposedly depicting mouse embryos and placentas from STAP cells and from embryonic stem cells were, in fact, both derived from STAP cells. Teruhiko Wakayama, a mouse cloning pioneer at the University of Yamanashi in Kofu who was the senior author on the letter, told Bioscience Technology in an e-mail that he spotted the problem with the images and informed RIKEN. (Wakayama did not respond to an e-mail from ScienceInsider seeking confirmation.) Obokata reportedly agreed to retract the letter, though it was not clear if this resulted from the discovery of the problem with the images. This week, there have been reports that genetic testing suggests the STAP cell lines were not derived from the mouse strains supposedly used in the experiments. Again, it is not clear if there is a connection to Obokata's decision to go along with retraction.

All the senior Japanese researchers are reportedly now in agreement with retracting the papers, but the position of Charles Vacanti, a tissue engineering specialist at Brigham and Women's Hospital in Boston, is unclear. Vacanti, the last author on the article, continued to defend the research until very recently. Typically, all authors must agree to a retraction, although in some cases, journals have gone ahead and retracted without every author's agreement.

"Nature does not comment on corrections or retractions that may or may not be under consideration," a Nature representative wrote in an e-mail to ScienceInsider today. "In general, retractions and corrections are not instantaneous, as they require consideration of the retraction or correction text from all authors."

Retraction will not be the end of the story. A group at RIKEN is trying to determine if the STAP phenomenon exists and can be reproduced. Kagaya says Obokata has been advising that group on her techniques. He could not verify if Obokata will actually join the group in its efforts, as Japanese media have reported. Other groups are known to be trying to determine if Obokata's group may have discovered some sort of artifact.

And there are still questions as to how such flawed papers got through the peer-review process. Several commentators have said that Nature needs to explain what went wrong.

"The science of the two papers was rigorously, robustly peer-reviewed as part of our usual editorial procedures. Any inaccuracies in the presentation of data that may have come to light since the peer review are being investigated," the Nature representative wrote. "We are always looking for ways to improve our processes to best serve the community and will continue to do so going forward."